Biomarkers are substances found in blood or other body fluids, in tissues or as receptors on cells that signal the presence or absence of a condition or disease, like cancer for instance. Biomarkers can be differentiated into predictive, prognostic and pharmacodynamics biomarkers.
Predictive biomarkers are used to assess the probability that a patient will respond to or benefit from a particular treatment. Prognostic biomarkers allow for the classification of tumours with regard to their aggressive potential to guide a decision of whom to treat or how aggressively to treat. Pharmacodynamic biomarkers measure the near-term treatment effects of a drug on the tumour and might be used to guide dose selection during clinical development of a new anti-cancer drug.
Targeted therapies are treatments that work on a molecular level to stop a cancer from growing or spreading. In order to avoid unnecessary approaches, because such therapies are usually related to the use of very aggressive drugs, there is a need for tools allowing to predict whether a patient will respond to a targeted therapy or not.
With regards to the fact that therapies become more and more target specific, the role of biomarkers will increase. They will help to individualise therapeutic approaches and to open the way to individualised oncology. Even the possibility to distinguish a responder to a specific therapy from a non-responder will help to prevent that patients will be subject to unnecessary treatments.
A commonly known and well-approved treatment of cancer is chemotherapy. One major disadvantage of chemotherapy is the use of very aggressive pharmaceuticals causing severe side effects. In order to minimize these side effects many attempts have been undertaken to minimize dosage of chemotherapeutics like for instance combining chemotherapy with immune activating agents. One approach is the use of immune activating DNA.
So-called unmethylated CG sequences have been shown to activate the immune system very effectively (Krieg A M, Yi A K, Matson S, Waldschmidt T J, Bishop G A, Teasdale R, Koretzky G A, Klinman D M; CpG motifs in bacterial DNA trigger direct B-cell activation; Nature 1995 Apr. 6 374:6522 546-9). Those sequences are derived from bacteria. EP 1 196 178 discloses a covalently closed circular DNA with partially self-complementary sequences resulting in a DNA construct having a double stranded stem with single stranded loops at both ends comprising the unmethylated CG motifs.
The combination of the dumbbell-shaped DNA constructs of EP 1 196 178 with chemotherapeutics to treat cancerous diseases has been proposed by EP 1 776 124. Patients who were treated with the DNA constructs of EP 1 196 178 received subsequently chemotherapeutic. It turned out that the amount of chemotherapeutic could be reduced by the disclosed combination. But this document does not disclose information about tools for identifying whether a patient will respond to the application of the combination therapy at all.
It is an object of the present invention to provide a method for predicting whether a cancer patient will respond to the treatment with immune activating DNA. Another object of the invention is the immune activating DNA itself, which can be used in such a method, i.e. to treat a patient identified as responder prior to the start of treatment